Abstract

Haemodialysis effectively removes small solutes and smaller-sized middle molecules from the blood; however, the clearance of larger middle molecules, which have been associated with negative effects, is poor. The novel medium cut-off (MCO) dialysis membrane has larger pore sizes and a more open structure than other high-flux membranes, providing improved removal of larger middle molecules while retaining albumin. However, larger pore sizes may potentially increase permeability to pyrogens, including endotoxins and other bacterial contaminants, that could be present in the dialysis fluid. In this study, we tested the capacity of low-flux, high-flux, MCO and high cut-off dialyser membranes with different pore sizes to prevent pyrogens crossing from dialysate to the blood side in a closed-loop test system, differentiating among lipopolysaccharides, peptidoglycans and bacterial DNA using a toll-like receptor assay. Even though the bacterial contamination levels in our test system exceeded the acceptable pyrogen dose for standard dialysis fluid, levels of lipopolysaccharides, peptidoglycans and bacterial DNA in the blood-side samples were too low to identify potential differences in pyrogen permeability among the membranes. Our results suggest that MCO membranes are suitable for haemodialysis using ISO standard dialysis fluid quality, and retain endotoxins at a similar level as other membranes.

Highlights

  • Microbial contamination of dialysis fluid can contribute to the pathological features of uraemia in patients receiving dialysis[1,2]

  • On the basis of calculated logarithmic retention values (LRVs), there were no significant differences among the retention capacities of membranes with different pore sizes when tested with E. coli LPS

  • Further analysis revealed a significant difference in the retention of LPS between medium cut-off (MCO) and low-flux membranes, MCO and high-flux membranes, and High cut-off (HCO) and low-flux membranes (Holm–Sidak pairwise comparison, p < 0.001, p = 0.009, and 0.041 respectively [Table 2]), with a higher LRV observed for the MCO and HCO membrane in all comparisons, that is the MCO and HCO membranes were less permeable than the other membranes, respectively

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Summary

Introduction

Microbial contamination of dialysis fluid can contribute to the pathological features of uraemia in patients receiving dialysis[1,2]. PGs are components of the bacterial cell wall of both Gram-positive and Gram-negative bacteria They are formed of complex heteropolymers and have a molecular weight of more than 20 kDa1,2,4,5. More sophisticated test systems are available that detect a wider range of contaminants derived from Gram-positive and -negative bacteria, such as LPS, PGs and bDNA, and mycoplasma, fungi and viruses. These assays exploit pattern-recognition receptors of the innate immune system to facilitate the detection of specific pathogens by recognizing highly conserved and class-specific molecules known as pathogen-associated molecular patterns[8]. Examples of these more versatile systems include the THP-19 and TLR assays[8]

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